Scope: Previous epidemiological studies on the association between circulating carotenoids and the risk of colorectal cancer drew inconclusive conclusions. This study aimed to examine serum carotenoids in relation to colorectal cancer risk in a Chinese population. Methods and results: One case-control study beginning from July 2010, consecutively recruited 538 eligible colorectal cancer cases and 564 age (5-year interval) and sex frequency-matched controls. Serum levels of alpha-carotene, beta-carotene, beta-cryptoxanthin, lycopene and lutein/zeaxanthin were detected by HPLC. Unconditional logistic regression was used to estimate the odds ratio (OR) and 95% confidence internal (CI) after adjusting for various confounders. Serum levels of alpha-carotene, beta-cryptoxanthin and lycopene were found to be inversely associated with colorectal cancer risk. The adjusted ORs of the highest quartile relative to the lowest quartile serum level were 0.49 (95% CIs 0.33-0.72) for alpha-carotene, 0.44 (95% CIs 0.29-0.66) for beta-cryptoxanthin, and 0.36 (95% CIs 0.24-0.54) for lycopene, respectively. The association between serum beta-carotene, lutein/zeaxanthin and colorectal cancer risk was not statistically significant. Conclusion: The results indicated that the incidence of colorectal cancer was associated with lower serum levels of alpha-carotene, beta-cryptoxanthin and lycopene among Chinese population residing in Guangdong.